Dimethylformamide → (+/-)-2-Amino-1-cyclopentyl-7-(3,4-dihydroxy-3-methylbut-1-yn-1-yl)-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

15 g of 2-amino-7-chloro-1-cyclopentyl-N-methyl-4-oxo-1,4-dihydro[1,8]-naphthyridine-3-carboxamide (53.44 mmol) and 11.11 g of (±)-2-methylbut-3-yne-1,2-diol (83.39 mmol) are introduced successively into a mixture of 267 ml of dimethylformamide and 104 ml of triethylamine in a 500 ml three-necked flask. The reaction mixture is sparged with argon for 15 minutes and then 1.02 g of CuI (5.34 mmol) and 1.87 g of bis(triphenylphosphine) palladium(II)dichloride (2.67 mmol) are successively added. The reaction mixture is heated for 30 minutes at 100° C. and then concentrated under reduced vacuum. The residue is taken up in a chloroform/water mixture and the insoluble material is filtered off. 20 g of a solid are obtained, which is purified by silica chromatography (solid deposit after solubilization in a tetrahydrofuran/methanol mixture and then elution with a dichloromethane/methanol gradient, 99:1 to 80:20) so as to give 7.5 g of expected product in the form of a beige solid.

Provenance & Evidence